The clinical and pathologic features of 109 cases of respiratory bronchiolitis (RB) identified from review of 156 consecutive surgical lung biopsy specimens were studied. A total of 107 of the 109 cases (98%) occurred in smokers, including all 83 current smokers and 24 of 49 ex-smokers (49%). RB persisted in some patients for many years after stopping smoking, occurring in one third of patients 5 years after quitting, and in one patient 32 years afterwards. A correlation was found between degree of cytoplasmic pigmentation of macrophages and number of pack-years smoked and also between the presence of peribronchiolar fibrosis and number of pack-years. No correlation was found between pulmonary function test results and pathologic findings. A desquamative interstitial pneumonia-like reaction was observed in six individuals. One patient each with a desquamative interstitial pneumonia-like reaction and one with RB were diagnosed based on clinical findings with desquamative interstitial pneumonia and RB-associated interstitial lung disease, respectively. No histologic features distinguished desquamative interstitial pneumonia from a desquamative interstitial pneumonia-like reaction or RB-associated interstitial lung disease from RB. Five cases of variant RB were encountered that resembled RB except that macrophage cytoplasm lacked pigment. All occurred in never-smokers, and their significance is unknown. RB is an accurate histologic marker of cigarette smoking, and it may be found many years after smoking ceases. There are no reliable histologic features to distinguish RB-associated interstitial lung disease from RB or desquamative interstitial pneumonia-like reactions from desquamative interstitial pneumonia.